TY - JOUR
T1 - Feasibility and impact of haplogroup matching for mitochondrial replacement treatment
AU - Takeda, Yuko
AU - Hyslop, Louise
AU - Choudhary, Meenakshi
AU - Robertson, Fiona
AU - Pyle, Angela
AU - Wilson, Ian
AU - Santibanez-Koref, Mauro
AU - Turnbull, Douglass
AU - Herbert, Mary
AU - Hudson, Gavin
N1 - Funding Information:
MH and GH are supported by the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z). LH (ICA Clinical Lectureship, ICA‐CL‐2017‐03‐010) was funded by Health Education England (HEE)/National Institute for Health Research (NIHR).
Publisher Copyright:
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2023/10/9
Y1 - 2023/10/9
N2 - Mitochondrial replacement technology (MRT) aims to reduce the risk of serious disease in children born to women who carry pathogenic mitochondrial DNA (mtDNA) variants. By transplanting nuclear genomes from eggs of an affected woman to enucleated eggs from an unaffected donor, MRT creates new combinations of nuclear and mtDNA. Based on sets of shared sequence variants, mtDNA is classified into ~30 haplogroups. Haplogroup matching between egg donors and women undergoing MRT has been proposed as a means of reducing mtDNA sequence divergence between them. Here we investigate the potential effect of mtDNA haplogroup matching on clinical delivery of MRT and on mtDNA sequence divergence between donor/recipient pairs. Our findings indicate that haplogroup matching would limit the availability of egg donors such that women belonging to rare haplogroups may have to wait > 4 years for treatment. Moreover, we find that intra-haplogroup sequence variation is frequently within the range observed between randomly matched mtDNA pairs. We conclude that haplogroup matching would restrict the availability of MRT, without necessarily reducing mtDNA sequence divergence between donor/recipient pairs.
AB - Mitochondrial replacement technology (MRT) aims to reduce the risk of serious disease in children born to women who carry pathogenic mitochondrial DNA (mtDNA) variants. By transplanting nuclear genomes from eggs of an affected woman to enucleated eggs from an unaffected donor, MRT creates new combinations of nuclear and mtDNA. Based on sets of shared sequence variants, mtDNA is classified into ~30 haplogroups. Haplogroup matching between egg donors and women undergoing MRT has been proposed as a means of reducing mtDNA sequence divergence between them. Here we investigate the potential effect of mtDNA haplogroup matching on clinical delivery of MRT and on mtDNA sequence divergence between donor/recipient pairs. Our findings indicate that haplogroup matching would limit the availability of egg donors such that women belonging to rare haplogroups may have to wait > 4 years for treatment. Moreover, we find that intra-haplogroup sequence variation is frequently within the range observed between randomly matched mtDNA pairs. We conclude that haplogroup matching would restrict the availability of MRT, without necessarily reducing mtDNA sequence divergence between donor/recipient pairs.
KW - haplogroup matching
KW - mitochondrial disease
KW - mitochondrial replacement therapy
UR - https://www.scopus.com/pages/publications/85168316623
U2 - 10.15252/embr.202154540
DO - 10.15252/embr.202154540
M3 - Article
C2 - 37589175
AN - SCOPUS:85168316623
SN - 1469-221X
VL - 24
JO - EMBO Reports
JF - EMBO Reports
IS - 10
M1 - e54540
ER -